1. Field of the Invention
The present invention relates to a novel 1,4-dihydropyridine-5-phosphonic acid cyclic ester, a process for the preparation thereof, and an antihypertensive agent or coronary or peripheral vasodilator composition containing the novel ester or its pharmaceutically acceptable salt.
2. Description of the Prior Art
1,4-Dihydropyridines are known to be useful for the medical treatment of coronary heart diseases, cerebral diseases, hypertension or arrhythmia, as they are capable of inhibiting the contraction of smooth muscle and cardiac muscle by calcium antagonistic effects (see A. Fleckenstein, Annu. Rev. Pharmacol. Toxicol., 17, 149-166 (1977)). However, the majority of 1,4-dihydropyridines known or being developed are substituted at the 3- and 5-positions by a carboxylic acid ester group.
Dihydropyridine-5-phosphonate derivatives are disclosed in prior art references. However, none of these references suggests or indicates the specific compounds of the present invention.
Relevant references are as follows: A. I. Razumov et al. synthesized a dihydropyridine-4-alkyl-5-phosphonate derivative (Zh. Obshch. Khim., 47, 1190-1191 (1977) and ibid., 51, 547-552 (1981)). Further, Von K. Issleib et al. synthesized 1,4-dihydropyridine-4-aryl-5-phosphonates (more specifically, diethyl 2,6-dimethyl-4-phenyl-3-ethoxy carbonyl-1,4-dihydropyridine-5-phosphonate and diethyl 2,6-dimethyl-4-(4-methoxyphenyl)-3-ethoxy carbonyl-1,4-dihydropyridine-5-phosphonate) (J. Prakt. Chem., Vol. 318, 207-220 (1976)). None of these references indicates the pharmacological activities. Furthermore, U.K. Patent Application GB No. 2105989A discloses a wide range of 1,4-dihydropyridine-5-phosphonate derivatives by a general formula, and teaches that the compounds represented by the general formula have cardiac activities. However, the specification of this Patent Application discloses no actual examples for the syntheses of 1,4-dihydropyridine-5-phosphonate derivatives and no pharmacological data relating to such derivatives.